Multi-dimensional cross-reactive array for chemical sensing

ABSTRACT

The discrimination ability of a chemical sensing cross-reactive arrays is enhanced by constructing sensing elements in two dimensions, first in the x-y plane of the substrate, second in the z dimension so that the sensors are vertically stacked on top of one another. Stacking sensing elements on top of one another adds to the discrimination ability by enabling the characteristic measurement of how fast target chemicals are passing through the stack of sensors. The new invention also allows the ability to discriminate components in a sample mixture by separating them using their innate difference in diffusional rates. Multi-sensor response patterns at each z level of sensors and time delay information from the sample passing from one level to the next are used to generate the response vector. The response vector is used to identify individual component samples and components in a mixture sample.

GOVERNMENT INTEREST

The invention described herein may be manufactured, used, sold,imported, and/or licensed by or for the Government of the United Statesof America.

FIELD OF THE INVENTION

This invention relates in general to cross-reactive arrays for chemicalsensing, and more particularly to multi-dimensional cross-reactivearrays for sensing explosive threats, chemical warfare agents, and toxicindustrial chemicals.

BACKGROUND OF THE INVENTION

A cross-reactive array sensor is a device that mimics the sense of smellin mammals. It is generally thought that mammal's sense of smell, whichis called olfaction, operates by the brain interpreting a complexpatterned response from the olfactory bulb where odors interact withbetween 800-1200 different receptors. Each receptor in the olfactorybulb is slightly different so that when they all interact with the sameodor they all respond slightly different making a pattern that ischaracteristic of that odor. Due the different chemical nature of eachodor the olfactory bulb makes a unique pattern for each odor that isable to be distinguished.

Cross-reactive arrays mimic the sense of smell by using more than onebroadly responsive (non-specific) chemical sensor to generate apatterned response which is then interpreted by a computer algorithm toidentify the chemical being interrogated. These have been made usingmany different sensing methods including tin oxide sensors, carbon blackpolymer composites, fluorescent polymers, carbon nanotubes, inorganicdyes, quantum dots, functionalized metallic nanoparticles, and others. Afew good references on these type of devices are, e.g., Anzenbacher,Jr., P., Lubal, P., Buček, P., Palacios, M. A. & Kozelkova, M. E. Apractical approach to optical cross-reactive sensor arrays. Chem. Soc.Rev. 39, 3954 (2010); and Albert, K. J. et al. Cross-Reactive ChemicalSensor Arrays. Chem. Rev. 100, 2595-2626 (2000).

All of the previous examples of cross-reactive arrays placed the sensingelements on the same plane where they interact with the sample.Additionally, all cross-reactive arrays are poor at identifyingcomponents in a mixture sample. This invention is similar but differentthan U.S. Pat. No. 7,189,353 B2. U.S. Pat. No. 7,189,353, entitled, “Useof spatiotemporal response behavior in sensor arrays to detect analytesin fluids,” discloses a time delay feature added to the feature vectorfor added discrimination ability and components in a mixture cantheoretically be discriminated.

Other references worth mentioning are Cross-reactive sensors, U.S. Pat.No. 7,250,267 B2 issued to Walt et al.; and Method for determininganalyte concentration by cross-reactivity profiling, U.S. Pat. No.5,338,659 A issued to Kauvar et al.

SUMMARY OF THE INVENTION

The disclosure relates to fabricating a chemical sensor that can be usedby the Army to sense explosive threats, chemical warfare agents, andtoxic industrial chemicals. It may be used by the food and beverageindustries in quality control relating to spoilage, ripeness, anduniformity of a manufactured item. The disclosure may also findrelevance in medical uses as a diagnostic tool for detecting disease.

Other devices of this type are referred to as cross-reactive arrays,electronic noses, and multiplexed sensors. Cross-reactive arrays aredisclosed with out-of-plane stacking of sensors to generatetime-dependent responses, which are then combined with different z-levelarray descriptors. Additionally, diffusion of volatile chemicals throughsolid medium is much slower than through gas or liquid, making aneffective device for identifying mixture samples much smaller. Thedevice is smaller because a slower diffusion rate makes the distanceneeded to separate components in a mixture much shorter.

Methods of making artificial olfactory systems rely on non-specificsensors which respond in concert generating a pattern that can beidentified as the odorant impinging upon the sensor. The responsepattern is formed by using chemically different sensors whose responseto a single analyte is varied. The difference of the sensors on themolecular level generates the varying changes in the transduction, andfeatures such as total magnitude of response, percent change ofresponse, and amount of spectral change are used to make the descriptivepattern response.

This invention adds more descriptive information to the response patternby arranging the elements of a cross-reactive array in a 2 dimensionalmanner, the first dimension is the direction of the sample flow in thesensor so that the sample interacts with each sensor in a sequentialmanner through the gas or liquid sample carrier medium. The firstdimension is in the x and y plane of the substrate that the device isconstructed on. The stacking of the sensors happens in the z dimensionof the substrate. The sensors are stacked in intimate contact one on topof another so that the only way for a sample to interact with underlyingsensors it to pass through the sensor on top of it. The stacking of thesensors adds a time dependent response to the underlying sensors basedupon the diffusion the sample through the sensor layers. The diffusiontime of the samples through the sensor is based upon the thickness ofthe sensor layers, density of the sensor layer, and chemicalinteractions that take place. The information added to the responsepattern is the diffusion constants, and difference in time it takes foreach sensor to respond. The diffusion constant and time delay are twocharacteristic features that can be added to the response pattern fordiscrimination.

This type of device can be constructed with any of the previouslyreported sensor types that are permeable to volatile chemicals.

BRIEF DESCRIPTION OF THE DRAWINGS

Additional advantages and features will become apparent as the subjectinvention becomes better understood by reference to the followingdetailed description when considered in conjunction with theaccompanying drawings wherein:

FIG. 1 shows an exemplary 2-dimensional cross-reactive array having asensor substrate in an enclosure.

FIG. 2 shows an exemplary z-dimensional stacking of sensor elements.

FIG. 3 shows a schematic of an exemplary three polymer system excitationusing a light source such as a 365 nm LED.

FIG. 4 shows exemplary spectral bands of three fluorescent polymersystem.

FIG. 5 shows exemplary z-stacked sensors in which a non-responsivepermeable buffer layer is added in between sensor layers.

FIG. 6a shows exemplary stacked sensor layers spaced in the x and ydirection by impermeable blocking layers.

FIG. 6b shows an alternate stacking sensor layering in which successivesensor layer each completely covers the sensor layer below.

DETAILED DESCRIPTION

Methods of making artificial olfactory systems (cross-reactive arrays)rely on non-specific sensors which respond in concert generating apattern that can be identified as the odorant impinging upon the sensor.The response pattern is formed by using chemically different sensors whoresponse to a single analyte is varied. The difference of the sensors onthe molecular level generates the varying changes in the transductionand features such as total magnitude of response, percent change ofresponse, fitting of polynomial lines, and amount of spectral change areused to make the descriptive response patterns.

This invention adds more descriptive information to the response patternby arranging the elements of a cross-reactive array in a 2 dimensionalmanner, the first dimension is the direction of the sample flow in thesensor so that the sample interacts with each sensor in a sequentialmanner through the gas or liquid sample carrier medium. This is shown inFIG. 1 where 1 the sensor substrate which can be quartz for opticalbased sensors or silicon for electrical based sensors is in an enclosure2. The areas where the stacks of sensor elements are laid out so thatthe flow interacts with them sequentially in the flow path are show aselements 3-8. The first dimension is in the x and y plane of thesubstrate that the device is constructed on. The stacking of the sensorshappens in the z-dimension of the substrate shown in FIG. 2 whereelements 9-14 are stacks of sensing elements. In this exemplaryembodiment, the sensors are stacked in intimate contact one on top ofanother so that the only way for a sample to interact with underlyingsensors is to pass through the sensor on top of it. The stacking of thesensors adds a time dependent response to the underlying sensors basedupon diffusion of the sample through the upper sensor layers. Thesensors in each z-stack have to be responsive to the same classes ofchemicals so that the passage of a chemical from one layer to the nextcan be measured. Each sensor in the z-stacked also needs to beindividually addressable so each one can be monitored for changes overtime. A way to make a stack of individually addressable stacked sensorsis to use fluorescent polymers whose emission intensity is dependent ontheir local environment. Each of the fluorescent polymers in the z-stackhave to have emission spectrums that are spectrally separated enough tomonitor each emission peak with a spectrometer. An example of this typeof fluorescent polymer z-stack are these three polymers;Poly[2,5-bisoctyloxy)-1,4-phenylenevinylene] (P1) with a emissionbetween 540-560 nm, Poly(9,9-dioctylfluorene-alt-benzothiadiazole) (P2)with emission between 515-535 nm andPoly[(9,9-dihexylfluoren-2,7-diyl)-co-(anthracen-9,10-diyl)] (P3) withemission between 450-435 nm. This three polymer system is also excitablewith a common light source such as a 365 nm LED. A schematic of thisdevice is in FIG. 3, where 15 is an excitation light source such as a365 nm LED. The light source 15 is focused onto the polymers P1-P3causing them to emit fluorescence which is collected by an opticalsystem such as a fiber optic cable seen as elements 16-21 which passesthe emitted light from each stack of sensors to a separate spectrometerelements 22-27. All of the spectrometers are connected to a computerelement 28 which is used to select wavelength bands from eachspectrometer output characteristic of each fluorescent polymer in thesensor stacks for each stack throughout the array. The spectrumsmeasured by each spectrometer and the selected spectral bands of thisthree fluorescent polymer system are shown in FIG. 4. Where elements29-31 are the fluorescence emission spectrums of P1-P3 respectively. Thebands which are monitored to characterize the different fluorescentpolymers are indicate in elements 32-34. In addition to these polymersbeing individually addressable with a spectrometer they are sostructurally different enough to provide a robust cross-reactive arrayresponse.

A second method of making a z-stack of fluorescent sensors is to use afluorescent nanocrystal/polymer composite. Fluorescence emission fromnanocrystals is a size dependent property with narrow emissionspectrums. The nanocrystals narrow emission spectrums allow more sensorsto be stacked in the z-direction and still be able to be spectrallyresolved using a spectrometer. A z-stack sensor array can be constructedusing a set of CdSe nanocrystals of sizes 2.2, 2.5 3.3, 4.5 nm withemission maxima of 480, 520, 560, 600 nm respectively in the same manneras FIGS. 3 and 4. This set of nanocrystal can then be mixed with anynon-fluorescent polymer to add chemical diversity such as this set,Poly(vinyl stearate), Poly(benzyl methacrylate), Poly(methylmethacrylate), Poly(ethylene-co-vinyl acetate). Each stack of sensors inmust only contain one composite of each size nanocrystal so thatdifferent layers of the stack can be monitored independently.

A third way of making individually addressable sensor is to use a stackof chemiresistors with insulating buffer layer in between them. Anexample of chemiresistor chemical sensor suitable for z-stacking includemodified carbon nanotubes, carbon nanotube polymer composites, andpolymer carbon black composites.

In all iterations of z-stacked sensors a non-responsive permeable bufferlayer can be added in between the sensor layer to increase the migrationtime between sensors as seen in FIG. 5. Where elements 35, 37, 39, 40,42, and 44 are sensors and elements 36, 38, 41, and 43 are permeablebuffer layers. The buffer layers increase the resolution ofmulti-analyte samples by increasing the time selective differentialpartitioning happens between sensors. Buffer layers can include neatforms of the polymers used in the sensing composites or other types ofpolymers such as siloxanes used in gas chromatography. The diffusiontime of the samples through the sensor is based upon the thickness ofthe sensor layers, density of the sensor layer, chemical interactionsthat take place, and the time added for the sample to pass through thebuffer layer.

There are several methods for constructing an array of z-stacked sensorsincluding, stamping, thermal evaporation, and inkjet printing. Stampingof the fluorescent polymer and polymer composite materials is done witha polydimethlsiloxane made with Dow Corning Sylgard 184 with is castonto a template of the desired sensor size and allowed to cure. Thecured stamp then has the fluorescent polymer or polymer composite spuncast onto it from a solvent. The solvent is evaporated from the stampleaving a layer of the sensing material. The inked stamp is then placedsensor side down on the sensor substrate and heated above the glasstransition temperature of the polymer. The stamp is then removed fromthe substrate leaving behind the sensor layer. This stamping process isrepeated with different sensing layers in the same location on thesubstrate to form the z-stacked sensor array. Stamping can also be usedto create the buffer layers between the sensor layers. It is ideal tohave the sample chemicals enter the z-stack from the top of the stackand not from the side walls of the stack. To prevent unwanted intrusionin the sensor stack two methods can be used with stamping. First, is tostamp sensor layers between an impermeable blocking layers that aredefined by photolithograph which are impermeable to the chemicals thatare being sensed. The second method is to construct the layers in amanner where the over coating layers are larger in size and fully coverthe underlying layers eliminating any sidewalls. These two methods areseen in FIGS. 6a and 6b , where in FIG. 6a , 45 and 46 are stackedsensor layers and in intimate contact with them in the x and y directionare elements 42-44 which are impermeable blocking layers. In FIG. 6b theclosest sensor layer to the substrate 47 is then completely covered bythe next sensor layer 48 which is then completely covered the nextsensor layer 49 until the desired number of sensor layer is achieved.

Thermal evaporation of sensing layer can be achieved by multipledepositions of the sensing material on top of one another. The positionsof the sensing material is defined by shadow masking the sensorsubstrate.

Inkjet printing can also create stacked sensor layer structures by usingan immiscible solvent system with a buffer layer between sensors. Thisprocess involves printing the first layer such as a fluorescent polymerin an organic solvent like Chloroform. The next layer deposited wouldthen need to be in a solvent that will not perturb the underlying layersuch as a water solution of poly(diallydimethylammonium chloride). Thisprocess of immiscible solvent layers is then repeated until the desirednumber of sensor layer is achieved.

This system operates with a flow path of gas or liquid above the arrayof stacked sensors. Into that flow path pulses of samples are introducedto interact with the sensor. The sensors at each z level are monitoredin the same manner as traditional cross-reactive arrays where eachsensor's response in the array is analyzed, selecting characteristicfeatures from it. The features from each sensor are then aggregated tocreate a feature vector. The feature vector is then compared to knownfeature vectors to make sample identification. This invention bystacking sensor elements adds new information to the feature vector thatwas previously not measureable. The new information is difference intime from when vertically adjacent sensors start to respond. This timeis characteristic of how long it took of the analyte to pass through thetop sensor. The information added to the response pattern is thediffusion constants, and difference in time it takes for each sensor torespond. The diffusion constant and time delay are two characteristicfeatures that can be added to the response pattern for discrimination.The addition of non-responsive buffer layer between the sensor layersallows for tuning the time differential for chemicals passing throughthe stack of sensors improving the array discriminating ability. Alsoincreasing the resolving power for multicomponent samples.

It is obvious that many modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims, theinvention may be practiced otherwise than as described.

What is claimed is:
 1. An enclosed cross-reactive array for chemicalsensing, comprising: a cross-reactive array, comprising a flat sensorsubstrate having an upper surface of stack areas, and stacks offluorescent chemical sensing polymer layers disposed on the uppersurface of the sensor substrate, wherein the fluorescent chemicalsensing polymer layers of a given stack are sequentially stacked suchthat each stack of fluorescent chemical sensing polymer layers risesfrom a respective stack area as a unique sequence of fluorescentchemical sensing polymer layers perpendicular to the surface of the flatsensor substrate, each stack resulting in a uniquely sequenced stack offluorescent chemical sensing polymer layers having a respectivelyexposed upper sensor layer, each fluorescent chemical sensing polymerlayer being respectively chosen from a group of fluorescent chemicalsensing polymers consisting ofPoly[2,5-bisoctyloxy)-1,4-phenylenevinylene],Poly(9,9-dioctylfluorene-alt-benzothiadiazole), andPoly[(9,9-dihexylfluoren-2,7-diyl)-co-(anthracen-9,10-diyl)], eachfluorescent chemical sensing polymer in the group characterized by aunique fluorescent emission spectrum having a distinct emission peak;and an enclosure enclosing the cross-reactive array, but having openends such that a carrier medium carries a chemical sample across thesequentially laid out stack areas on the surface of the flat sensorsubstrate from one open end to another open end of the enclosure.
 2. Themulti-dimensional cross-reactive array as recited in claim 1, whereinsaid flat sensor substrate is comprised of quartz for optical basedsensors or silicon for electrical based sensors.
 3. Themulti-dimensional cross-reactive array as recited in claim 1, whereinsaid carrier medium is either a gas or liquid sample carrier medium. 4.The multi-dimensional cross-reactive array as recited in claim 1,comprising a non-responsive permeable buffer layer disposed between thefluorescent chemical sensing polymer layers to increase a migration timebetween sensors.
 5. The multi-dimensional cross-reactive array asrecited in claim 1, wherein the fluorescent chemical sensing polymerlayers are stacked by stamping of fluorescent polymer materials.
 6. Themulti-dimensional cross-reactive array as recited in claim 1, whereinthe fluorescent chemical sensing polymer layers are stacked by inkjetprinting of fluorescent chemical sensing polymer layers with a bufferlayer between stacked fluorescent chemical sensing polymer layers.
 7. Achemical sensing device based on an enclosed cross-reactive arrayaccording to claim 1, comprising: the cross-reactive array of claim 1; alight source focused onto the multi-dimensional cross-reactive array tocause each of the stacked fluorescent chemical sensing polymer layers toemit a respective fluorescence; an optical system based on fiber opticcables for passing the respectively emitted light from each stack offluorescent chemical sensing polymer layers to a respective spectrometerelements to produce a respective spectrometer output; and a computingdevice connected to receive and process each spectrometer output forselect wavelength bands to characterize each fluorescent chemicalsensing polymer layer in the stack associated with the respectivespectrometer output throughout the array.
 8. The chemical sensing deviceas recited in claim 7, wherein the light source is comprised of a 365 nmLED.